Almost nine years ago, in January 2014, the Federal Government instituted the National Policy for Total Care for People with Rare Diseases, which reinforces the right to free total care for people with rare diseases within the Unified Health System (SUS). The offer of this care, in some cases, should start when the couple plans a pregnancy, with the advice of a medical geneticist. However, of the 322 geneticist doctors in Brazil, only 10 are based in the Amazon, according to the professionals' registry at the Federal Council of Medicine (CFM). Therefore, this follow-up is not always possible for the families in the region.

Considering that about 80% of rare diseases are of genetic origin, genetic counseling should be done with a medical geneticist, who assesses whether there is risk of a genetic disease occurring in a family and, together with a multi-professional team, guides when there is already a case in the family, explaining how to deal with this scenario. During prenatal care, this follow-up is indicated for couples who have a consanguineous relationship (among relatives), or a history of fetal loss (when the baby is lost during pregnancy) and also when there is someone with a rare disease in the family.

However, the percentage of medical geneticists represents only 3.10% of the national total. And the only three states in Brazil that do not have this specialty are in the region: Amapá, Roraima, and Tocantins - these, along with Rondônia, also do not have any specialized public care services. To have an idea of the regional inequality, the 10 doctors who work in the Amazon are equivalent to 10% of the total number of professionals in São Paulo, the state with the largest number of doctors with this specialty (100 professionals registered in the CFM).

Maria Juliana Rodovalho is one of those who are part of this select regional group. She is today one of the three geneticist doctors who work in Maranhão, but, for a long time, she was the only one to work in the state. "I spent 14 years as the only medical geneticist here, I had only a few professionals who came, sporadically, and others were seen by telemedicine, with doctors from other states. Even so, the first challenge I faced was to be incorporated into the job market", she recalls.

When she started her career, she noticed little interest from public hospital managers in incorporating this specialty. Even now, Juliana says that there are no medical geneticists working in Maranhão with a career plan, through public exams. She provides services to the Health Secretariat as a legal entity and, through her company, she invited another medical geneticist to be a partner and to share the services. "There is a lack of structure in the public service for hiring specialized professionals and training for those who work in Primary Care and are the first contact for the patient. And there is still a lack of incentive for medical students to enter the area", she says. Today, the residencies in Medical Genetics, necessary formation to become a specialist, are concentrated in the South and Southeast regions and, when passing through this stage, many professionals end up not returning to the Amazon to work, according to Rodovalho's perception.

Heel prick test is an important ally for diagnosis

Long before the 2014 Ordinance, the so-called "Teste do Pezinho" (Heel prick test) already existed in SUS, incorporated into the system in 1992. It is a neonatal screening, a right of all children born in Brazil, and is a preventive test done by collecting drops of blood from the feet of newborns, performed in maternity hospitals and health units throughout the country. The test investigates at least six rare diseases: phenylketonuria and other hyperphenylalaninemias, congenital hypothyroidism, sickle cell disease and other hemoglobinopathies, cystic fibrosis, congenital adrenal hyperplasia, and biotinidase deficiency. "These are diseases that manifest themselves in early childhood and can be treated, besides being highly reliable tests," says Rodovalho. The ideal is to perform the collection 48 hours after the beginning of breastfeeding, as soon as possible, although the neonatal period is up to 28 days and collections are accepted without medical request until this period.

Since 2021, the Federal Government has increased to 50 the number of diseases that can be detected by the Heel prick test offered by SUS. However, many health units are still not able to perform this list of tests. "For all screening tests, time is important because we need to detect the pathology as soon as possible so that the child has the least possible sequelae, or no sequelae at all, which is ideal, and does not die. We are waiting for the Ministry of Health to organize with the state secretariat the necessary structure to expand the test to more diseases," says Ana Thalyta Costa, a nurse from the Association of Parents and Friends of Exceptional Children (APAE) in São Luís (MA).

APAE São Luís is the Reference Service in the state, receiving the Heel prick test samples from all municipalities in Maranhão and performing the laboratory analysis.  Besides identifying the diseases, the federal program of neonatal screening recommends that, if the child is diagnosed with any of these conditions, it receives the appropriate treatment by SUS consecutively to the test result.

In Maranhão, this step is done in three different places - for some diseases, such as phenylketonuria, for example, the treatment is at APAE itself. "At APAE, we provide multi-professional support, with a geneticist doctor, nutritionist, psychologist, among other specialties, and we also provide rehabilitation services, such as therapies, prosthetics and wheelchairs, when necessary," explains Rosilene Cutrim, coordinator of the state's Newborn Screening Reference Service (SRTN), at APAE São Luís.

Institutions seek access to federal resources

The National Policy for Total Care for People with Rare Diseases determines that the health establishments may receive financial incentive from the Federal Government to offer exams, consultations with a multi-professional team, treatment, among other services that integrate the integral care and specialized attention to rare diseases.

With the qualification, the units can become a Reference Service in Rare Diseases or a Service of Specialized Attention in Rare Diseases and can receive up to R$41,480.00 per month. To do so, the establishment needs to prove that it has the technical conditions, physical facilities, equipment and human resources suitable for providing this service to patients, meeting a series of prerequisites to be able to plead for the qualification.

This is what APAE São Luís has been seeking. In Pará, the Bettina Ferro de Souza University Hospital is also trying to qualify. Together with Hospital Barros Barreto, the Bettina Ferro makes up the Hospital Complex of the Federal University of Pará (UFPA)/ Brazilian Company of Hospital Services (Ebserh), which centralizes all specialized care to rare diseases in the state.

Doctor Isabel Neves has been a pediatrician for 28 years at Bettina Ferro and, because of her dedication to children, she became closer and focused on working with rare genetic diseases. She is part of a multi-professional team at the hospital, which includes a medical geneticist. "The qualification at the federal level will make a big difference, because we will have the resources to ensure more complex exams, which today depend a lot on the research projects of the university itself and of the Evandro Chagas Institute, and sometimes need to be sent out of the state. We will also qualify the service, be able to hire more professionals, and better supply the patients' demand", she ponders.

In her experience, Isabel has closely followed the difficulties many patients have in accessing diagnosis and treatment, and has been engaged in the fight for improvements in quality of life for these people. "Sometimes the patients' journey from the first symptoms is very long; it can take years to reach a service that makes the correct diagnosis. With all the difficulties in the Amazon, even the logistical ones, we also need to ensure that there is a greater decentralization, that there are specialized services and trained professionals in the interior of the states", she declares.

For her, having qualified centers can also ensure that patients have follow-up in adulthood, because, in most cases in the region, the service is available in maternity hospitals and pediatric sections - as it is in the Bettina Ferro.

Universities fill gaps in the health system

Just as the Bettina Ferro depends on the partnership with the laboratories of the UFPA (Laboratory of Innate  Errors of Metabolism and Laboratory of Human and Medical Genetics) to perform the genetic tests of patients, in other states the reality is repeated.

In Rondônia, there is only one geneticist doctor, who attends in a private clinic, and no state reference center in the public health system. Thinking about the repressed demand, a group of researchers from the Federal University of Rondônia (UNIR) decided to expand a research project to also become an extension program, called "Caring for the rare", in 2016. "Until then, it was a research work. We followed up with families who had patients with rare diseases and, during home visits, we realized that their situation was so complex, so difficult, that we couldn't just stay in research, we needed to help as we could," says Professor Vivian Susi, a professor in UNIR's Human Genetics Laboratory and a member of the program.

The professor says that, in the absence of a state reference center, some patients get transfers through the public health system to undergo treatment in São Paulo, Goiânia and Porto Alegre. "But few people have this opportunity, most stay here and it is difficult because we see that their living conditions could be much better, with proper assistance," she adds.

According to her, the group took advantage of the field trips, with the initial goal of collecting data for studies, to also take social assistance actions, collection of material for laboratory tests, and other services to improve the quality of life and well-being of the patients. "Many patients live in rural areas, far from urban centers, and have difficulty accessing information and being part of SUS," she recalls.

Among the guidance provided is also the direction for families to get the Benefício de Prestação Continuada (BPC), a federal government guarantee that provides one minimum salary per month, to the elderly and to people of any age who have some condition that makes it impossible for them to participate "fully and effectively in society."

The activities strengthened in 2019, after the program received the donation of a van, which made it possible to expand home visits, even reaching municipalities in Amazonas and Rondônia. On each trip, a multiprofessional group followed, including professionals from Medicine, Biologists, Social Work, and Physical Education, and volunteers from Nutrition, Psychology, and Dentistry, among other specialties.

Besides the communities benefited by the project, UNIR's undergraduate and post-graduate students also gained with the initiative a space for learning in practice.

Budget cuts harmed actions

In the last two years, in addition to the impacts of the pandemic of social distancing and economic crisis, the federal budget cuts to universities made it impossible to advance the project and even to continue the activities that were already being done. "At the moment we are without supplies for the laboratory, which is an important part of the project, because it is where we analyze the samples and make diagnoses. We lost many of them during the pandemic because they expired and we still can't find the resources to buy them again," explains Professor Vivian Susi, from UNIR's Human Genetics Laboratory.

The Laboratory of Genetics and Molecular Biology (LabGeM) at the Federal University of Maranhão (UFMA) is going through a similar situation. There is state-of-the-art equipment available and trained professionals to perform tests such as the karyotype, which analyzes all the chromosomes present in a person's DNA and can detect conditions such as Turner's Syndrome, which happens when a woman is born with only one X chromosome (instead of two) and causes symptoms such as short stature.

However, the equipment is currently being used exclusively for research, as there are no resources to serve the community as a whole. The LabGeM coordinator, Silma Pereira, points out that, from 2002 to 2008, the laboratory opened its doors to meet the demands of the population, receiving referrals from UFMA's University Hospital. "I used the resources from my research projects to bring this service. Meanwhile, we tried with the University to seek agreements with the state and municipal health secretariats so that we could attend the patients in a more definitive way, but it never went ahead," she says. Until 2019, the professor performed some exams on her own. "The demand is there and it's very high. It's a pity we can't expand it for the population to enjoy," she believes.

Patients' families are important partners in the actions

In the Amazon states, rare disease patient associations play a fundamental role in multiplying qualified information and directing those who seek a reference service. The groups are usually organized by mothers and fathers who have learned on a daily basis how to deal with the pathologies and exchange experiences with each other. This is the case of Ligia Lopes, who is the mother of a Williams Syndrome patient, whose symptoms include unusual facial features, such as a smaller and more prominent nose than usual, as well as coordination and balance difficulties. In 2014, she founded the Para Williams Syndrome Association, which has grown over the years and now includes other rare diseases. "We have patients from more than 28 types of rare genetic diseases in the association and together we fight for guaranteed rights, fight for public policies and conduct lectures, home visits and other actions to support families," explains the founder.

The Association's performance was so important in the state that it mobilized the creation of a specific department for Williams Syndrome in the Bettina Ferro Hospital. "Through the mobilization of the mothers, we started to receive more and more patients likely to have the disease. They helped to give visibility and referral to people who might never receive the correct diagnosis and treatment, points out Isabel Neves, a doctor at the hospital.

Where to look for specialized attention in rare genetic diseases in the Amazon

ACRE

• Women's and Children's Health Care System (Sasmc) at the Hospital da Criança e Maternidade Bárbara Heliodora
• Outpatient Clinic of the Acre Hospital Foundation (FUNDHACRE)
• Rio Branco Cancer Hospital
• Specialized Rehabilitation Center (CER)
• Tucumã Polyclinic

AMAZONAS

• Adriano Jorge Hospital Foundation - FHAJ
• Genetic Counseling Clinic of the University Hospital - UFAM
• Genetic Medicine Outpatient Clinic of APAE Manaus

MARANHÃO

• Reference Service in Newborn Screening of Maranhão of the Association of Parents and Friends of the Exceptional of São Luís (Apae São Luís)
• Medical Genetics Service of the Maternity of High Complexity of Maranhão (MACMA)
• Medical Genetic Service of Juvêncio Mattos Children's Hospital

MATO GROSSO

• Medical Genetics Service of Júlio Müller University Hospital - UFMT

PARÁ

• Federal University of Pará Hospital Complex (UFPA)/ Brazilian Company of Hospital Services (Ebserh)

Amapá, Rondônia, Roraima and Tocantins do not have official specialized care services for genetic rare diseases. In these cases, treatment is guaranteed to patients through the Out-of-Domicile Treatment policy.

In the case of Tocantins, there is a technical group for rare and/or degenerative diseases, which prepares clinical protocols and/or studies with the presentation of an opinion regarding the feasibility of incorporating technology in health care at the state level.

Sources: Brazilian Society of Medical Genetics (SBGM), NGO Many We Are Rare (MSR) and state health secretariats.